Synthesis and actions of OHD

The most biologically active form of calciferol is 1,25-OHD and its synthesis is tightly controlled (Loveridge, 2000). The kidney produces both dihydroxylated forms of vitamin D (1,25 and 24,25-OHD); the dominant form is determined by

the circulating level of parathyroid hormone (PTH), plasma calcium concentrations and the current vitamin D status of the body. In response to PTH in the vitamin D-deficient state, 1,25-OHD production is high (and this directly induces feedback inhibition of PTH production within the parathyroid gland) and 24,25 OHD is low. In the vitamin D-adequate state, 1a-hydroxylase activity in the kidney is increased and more 24,25-OHD is produced. Again, 1,25-OHD directly reduces PTH production in the parathyroid gland (Fig. 3.2). Under most circumstances the principal site for 1,25-OHD production is the kidney; however, during pregnancy the placenta also seems to have a role in producing it at the time of increased calcium requirements by the foetus (Loveridge, 2000).

Vitamin D maintains plasma calcium concentrations by stimulating intestinal calcium absorption by the small intestine and/or the resorption of calcium from bone. Calcium transport across intestinal cells is stimulated by 1,25-OHD by inducing the production of calcium binding protein (CBP) within the villous cells, and inducing an extremely low concentration of cystolic calcium within the enterocyte. 1,25-OHD also promotes cell maturation within the intestine (Suda et al, 1990) and in studies using vitamin D-deficient rats, villous length is only 70% of that of normal rats. Serum calcium is tightly controlled but a number of studies suggest it peaks in the summer perhaps because of improved vitamin D status, growth stimulation in children and higher intestinal calcium absorption (McCance and Widdowson, 1943). More recent studies, using radio-isotopes, have shown fractional calcium absorption was significantly higher in post-menopausal women evaluated from August to October than from March to May (Krall and Dawson-Hughes, 1991). In addition, increased intestinal calcium retention was associated with a lower rate of bone loss from the radius. The changes in calcium absorption and excretion could be accounted for by small seasonal increases in 1,25 OHD during the summer months found in some of the studies (Sherman et al, 1990).

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